Process for preparing acylsulfamoylbenzamides

ABSTRACT

The invention relates to a process for the preparation of a compound of formula (I): 
                         
Which comprises reaction of a compound of formula (II) with a compound of the formula (III) in the presence of a chlorinating agent, followed by reaction of the resultant compound of the formula (IV) with a compound of formula (V) in the presence of a base:
 
                         
wherein the various symbols are as defined in claim  1.

This invention relates to the technical field of chemical processes forthe preparation of compounds, particularly a novel process for thepreparation of a wide range of acylsulfamoylbenzamides, which compoundsare useful, e.g. as safeners for pesticides.

The use of safeners is an increasingly valuable tool for extending thepractical utility of many types of pesticides, in particular herbicides,in crops of useful plants such as maize, rice, or cereals, particularlyin post-emergence application.

Patent Publication Number WO 99/16744 describes acylsulfamoylbenzamidederivatives and their use as safeners for the control of weeds byherbicides. The safened herbicide mixtures possess very desirableagronomic properties and may potentially of commercial utility.

Various processes are described for the preparation of these compoundsin the above publication, however these methods are not always veryefficient and generally require many reaction steps from readilyavailable starting materials. Consequently it is of value to develop anew process which does not suffer from these disadvantages and cantherefore be useful for industrial scale operations.

Two general processes for preparing acylsulfamoylbenzamide derivativesare described in WO 99/16744.

The first process described involves the acylation of asulfamoylbenzamide using a benzoic acid halide, anhydride orcarbonylimidazolide, or using a benzoic acid and a coupling agent suchas N,N-dicyclohexylcarbodiimide. A number of specific examples of thisprocess are described therein, which are carried out by heating amixture of a benzoic acid with the sulfamoylbenzamide,1,1′-carbonyldiimidazole and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) intetrahydrofuran. However this procedure is of limited value for largescale or industrial operations because of the moderate yields obtained,as well as the prohibitively expensive 1,1′-carbonyldiimidazole whichadditionally gives rise to substantial waste by-products.

The second general process described in the above reference involves thereaction of an activated acylsulfamoylbenzoic acid derivative with anamine, but this method is not specifically exemplified therein. Adisadvantage of this approach is that procedures for the preparation ofthe activated acylsulfamoylbenzoic acid derivative, such as the acidchloride derivative, are generally inefficient since many reaction stepsare involved, leading to poor or moderate overall yields.

In order to overcome the above limitations of the known processes wehave now developed a new two step process for the preparation ofacylsulfamoylbenzamide compounds, which involves a reduced number ofreaction steps and which is applicable to industrial scale processes.

According to the present invention there is provided a process for thepreparation of a compound of general formula (I):

wherein:R¹ is hydrogen, —(CH₂)_(p)-heterocyclyl or a hydrocarbon radical, wherethe two last-mentioned radicals are unsubstituted or substituted by oneor more radicals selected from the group consisting of halogen,(C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl, (C₁-C₆)-alkoxy, cyano and nitro;R² is hydrogen, (C₁-C₆)-alkyl, (C₂-C₆)-alkenyl, (C₂-C₆)-alkynyl,(C₁-C₆)-alkoxy, (C₂-C₆)-alkenyloxy, where the five last-mentionedradicals are unsubstituted or substituted by one or more radicalsselected from the group consisting of halogen, (C₁-C₄)-alkoxy and(C₁-C₄)-alkylthio; orR¹ and R² together with the linking nitrogen atom form a 3- to8-membered saturated or unsaturated ring;R³ and R⁵ are each independently halogen, (C₁-C₆)-alkyl,(C₁-C₆)-haloalkyl, (C₁-C₆)-alkoxy, S(O)_(q)—(C₁-C₆)-alkyl,(C₁-C₆)-alkylcarbonyl, —CO-aryl, cyano or nitro; or two adjacent R⁵groups form a —O—CH₂CH₂— moiety;R⁴ is hydrogen, (C₁-C₄)-alkyl, (C₂-C₄)-alkenyl or (C₂-C₄)-alkynyl;n is an integer from 0 to 4;m is an integer from 0 to 5;p is 0 or 1; andq is 0, 1 or 2; or a salt thereof; which process comprises:a) the reaction of a compound of general formula (II):

wherein R³, R⁴ and n are as defined in formula (I), with a compound offormula (III):

wherein R⁵ and m are as defined in formula (I) and Y is OH or Cl, in thepresence of a chlorinating agent, to give a compound of formula (IV):

wherein R³, R⁴, R⁵, m and n are as defined in formula (I), andb) the reaction of the compound of formula (IV) obtained in step a) witha compound of formula (V):R¹R²NH  (V)wherein R¹ and R² are as defined in formula (I).

The chlorinating agent used in the process is preferably selected from asulfur or phosphorous based chlorinating agent such as thionyl chloride,phosphorus oxychloride or phosphorus pentachloride, and a carbon basedchlorinating agent used for converting a carboxylic acid into thecorresponding acid chloride, such as oxalyl chloride or phosgene. Thepreferred chlorinating agent is thionyl chloride.

The amount of chlorinating agent used has an influence on the yield ofproduct of formula (IV) and can be optimised by way of preliminarytesting depending on the solvent, the amount and type of startingmaterial amongst other factors. In most cases the amount is betweenslightly below the stoichiometric amount up to an excess.

The amount of chlorinating agent used depends upon the definition of Yin formula (III), for example when Y is OH compounds of formula (IIIa):

are used as starting material. Alternatively when Y is Cl compounds offormula (IIIb):

are used.

When Y is OH, the amount of chlorinating agent used is preferably from 1to 2 molar equivalents per equivalent of carboxylic groups of compounds(II) and (IIIa), more preferably from 1.1 to 2 molar equivalents perequivalents of (II) and (III), most preferably from 1.2 to 1.9 molarequivalents per equivalents of (II) and (III). When Y is Cl, the amountof chlorinating agent used is preferably from 1 to 2 molar equivalentsper equivalent of compound (II), more preferably from 1.1 to 2 molarequivalents per equivalent of (II), most preferably from 1.2 to 1.9molar equivalents per equivalent of (II).

In reaction step a) the compound of formula (IV) can be isolated bycommon or customary methods, for instance preferably by partialevaporation during which it precipitates and may be filtered off.

In a further feature of the invention the unreacted excess chlorinatingagent, which in the case of thionyl chloride is present in thedistillate, may be recycled.

The ratio of (II):(IIIa) is preferably 1:1, but in some cases it isbeneficial to add a slight excess (up to 10%) of the acid (IIIa), whichhas the advantage of ensuring a more complete conversion of the acid(II) in the reaction. This variation is preferably used if thecorresponding acid chloride of formula (IIIb) remains soluble in thereaction mixture after partial evaporation, since separation from theprecipitated desired product (IV) is then effected.

A catalyst such as a N,N-dialkylacylamide, for exampleN,N-dimethylformamide or N,N-dibutylformamide, or a cyclic amine such aspyridine or quinoline is optionally also present in the reactionmixture.

The reaction can be conducted in the absence or preferably presence of astable and inert solvent, which can be an non-polar or a polar organicsolvent which essentially do not react with the chlorinating agent orthe compounds (III) or (IV) in the reaction mixture. It is for example anon-polar organic solvent which is preferably selected from

-   -   aliphatic or aromatic hydrocarbons such as alkanes, for example        heptane, octane, or an alkylated benzene such as toluene,        dimethylbenzenes (xylols) or trimethylbenzenes, or paraffin oil,    -   halogenated aliphatic hydrocarbons such as dichloromethane, or        halogenated aromatic hydrocarbons such as chlorobenzene or        dichlorobenzene, or haloalkylbenzenes such as benzotrifluoride,        and    -   silicon oils.

The most preferred solvents are chlorobenzene and toluene.

The reaction temperature in step a) may vary within wide limitsdependent on the solvent and pressure used. For example, the reactiontemperature is from 70° C. to 140° C., preferably from 80° C. to 130°C., more preferably from 80° C. to 115° C.

The reaction step a) generally proceeds in excellent yield, with typicalyields of the compound of formula (IV) in excess of 90% or even 95%. Thepurity of the compound of formula (IV) is generally very high (typicallyat least 95%).

The acid chloride derivative of formula (IIIb) above is formed as anintermediate in the preferred reaction where the compound of formula(IIIa) is used as starting material, and acylates the sulfamoyl moietyof the compound of formula (II) and/or its acid chloride derivative offormula (VI):

In contrast with the above-mentioned preparation of acylsulfamoylbenzoic acid chlorides from the corresponding benzoic acids of formula(III) via separate chlorination of the compound of formula (II),unwanted dimeric side-products are essentially avoided in the process ofthe invention.

The reaction of the compound of formula (IV) with the compound offormula (V) in step b) can be performed with or without an additionalbase. Preferably an additional base is used in which case it may be aninorganic base such as an alkali metal hydroxide or alkoxide, forexample sodium hydroxide, potassium hydroxide or sodium methoxide, or analkali metal carbonate such as potassium carbonate, sodium carbonate orlithium carbonate, or an alkali metal bicarbonate such as sodiumbicarbonate or potassium bicarbonate, or an alkali metal alkanoate suchas sodium acetate, or an alkaline earth metal hydroxide, carbonate orbicarbonate, or an organic base such as a trialkylamine for exampletriethylamine or tributylamine, or a N-dialkylaniline such asdimethylaniline.

The preferred additional base is triethylamine, potassium carbonate orsodium carbonate.

The amount of the additional base used can generally be varied withinwide limits and optimized by preliminary testing. Preferably the ratioof molar equivalents of additional base to molar equivalents of thecompound of formula (IV) is from 1.2:1 to 1:1.2, more preferablyequimolar amounts of base and compound (IV).

The amount of amine (V) used is preferably a small excess in relation tothe amount of (IV), typically about 1.05 molar equivalents of (V) for 1molar equivalent of (IV). It is also possible to use 2 molar equivalentsof the compound of formula (V) wherein one molar equivalent is utilisedas the base in the reaction.

The process step b) is typically carried out in the presence or absenceof a solvent.

When a solvent is used a wide variety of polar or non-polar solvents maybe employed, as long as they do not substantially react with thecompound of formula (IV). A number of solvents may be used, for examplearomatic hydrocarbons such as an alkylated benzene, for example toluene,or nitriles such as cyanoalkanes for example acetonitrile, orhalogenated hydrocarbons such as haloalkanes, for exampledichloromethane, or halogenated aromatic compounds such as halobenzenes,for example chlorobenzene, or ethers such as dialkyl ethers, for examplediethyl ether or diglyme, or cyclic ethers such as tetrahydrofuran ordioxan, or a N,N-dialkylacylamide such as N,N-dimethylformamide orN,N-dimethylacetamide, or a N-alkylpyrrolidinone such asN-methylpyrrolidinone. Nitrile solvents are preferred, most particularlyacetonitrile.

The reaction temperature for step b) is preferably from 0° C. to 150°C., more preferably from 0° C. to 60° C., most preferably from 10° C. to20° C.

The product of formula (I) can be isolated in a simple manner, forexample by dilution of the reaction mixture with water, followed byacidification with, for example a mineral acid such as hydrochloricacid, and filtration.

The isolated yield of the compound of formula (I) is generally veryhigh, typically in excess of 90% or even 95%. The product is generallyobtained in high purity, typically at least 95%.

The process of the invention, depending upon the chlorinating agent mayalso be carried out as a one-pot procedure. In this variation, reactionstep a) is preferably followed by removal (for example by evaporation)of remaining chlorinating agent, followed in the same pot by thereaction step b).

In a further feature of the invention there is provided a process forthe preparation of a compound of formula (IV) as defined above, by thereaction of a compound of formula (II) as defined above, with a compoundof formula (III), preferably compound (IIIa) as defined above, in thepresence of a chlorinating agent as defined above (preferably thionylchloride).

In a further feature of the invention there is provided a process forthe preparation of a compound of formula (IV) as defined above, by thereaction of a compound of formula (II) as defined above, with a compoundof formula (IIIb) as defined above in the presence of a chlorinatingagent as defined above (preferably thionyl chloride).

In a further feature of the invention there is provided a process forthe preparation of a compound of formula (I) as defined above, by thereaction of a compound of formula (IV) as defined above, with a compoundof formula (V) as defined above:

In the formula (I) and all the formulae hereinabove and hereinbelow, theterms mentioned have the meanings outlined below:

The term “halogen” includes fluorine, chlorine, bromine and iodine.

The term “(C₁-C₄)-alkyl” is to be understood as a straight-chain orbranched hydrocarbon radical having 1, 2, 3 or 4 carbon atoms, forexample the methyl, ethyl, propyl, isopropyl, 1-butyl, 2-butyl,2-methylpropyl or tert-butyl radical.

Correspondingly, alkyl radicals having a greater range of carbon atomsare to be understood as straight-chain or branched saturated hydrocarbonradicals which contain a number of carbon atoms which corresponds tothis range. The term “(C₁-C₆)-alkyl” thus includes the abovementionedalkyl radicals, and also, for example, the pentyl, 2-methylbutyl,1,1-dimethylpropyl and hexyl radical.

“(C₁-C₄)-haloalkyl” or “(C₁-C₆)-haloalkyl” are to be understood as analkyl group mentioned under the term “(C₁-C₄)-alkyl” or “(C₁-C₆)-alkyl”respectively in which one or more hydrogen atoms are replaced by thecorresponding number of identical or different halogen atoms, preferablychlorine or fluorine, such as the trifluoromethyl, the 1-fluoroethyl,the 2,2,2-trifluoroethyl, the chloromethyl, fluoromethyl, thedifluoromethyl and the 1,1,2,2-tetrafluoroethyl group.

“(C₁-C₄)-alkoxy” or “(C₁-C₆)-alkoxy” are to be understood as an alkoxygroup whose hydrocarbon radical has the meaning given under the term“(C₁-C₄)-alkyl” or “(C₁-C₆)-alkyl” respectively. Alkoxy groups embracinga larger range of carbon atoms are to be understood likewise.

The terms “alkenyl” and “alkynyl” having a prefix stating a range ofcarbon atoms denote a straight-chain or branched hydrocarbon radicalhaving a number of carbon atoms corresponding to this range, thishydrocarbon radical having at least one multiple bond which can be inany position of the unsaturated radical in question. “(C₂-C₆)-alkenyl”thus denotes, for example, the vinyl, allyl, 2-methyl-2-propenyl,2-butenyl, pentenyl, 2-methylpentenyl or the hexenyl group.“(C₂-C₆)-alkynyl” denotes, for example, the ethinyl, propargyl,2-methyl-2-propynyl, 2-butynyl, 2-pentynyl and the 2-hexynyl group.

“(C₃-C₈)-cycloalkyl” denotes monocyclic alkyl radicals, such as thecyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl orcyclooctyl radical and bicyclic alkyl radicals, such as the norbornylradical.

“(C₃-C₈)-cycloalkoxy” or “(C₃-C₈)-cycloalkylthio” is to be understood asone of the abovementioned (C₃-C₈)-cycloalkyl radicals which is attachedvia an oxygen or sulfur atom.

“(C₁-C₄)-alkylthio” or “(C₁-C₈)-alkylthio” respectively are an alkylthiogroup whose hydrocarbon radical has the meaning given under the term“(C₁-C₄)-alkyl” or “(C₁-C₆)-alkyl”.

Other composite terms, such as (C₃-C₆)-cycloalkenyl are to be understoodcorrespondingly, in accordance with the above definitions.

The term “aryl” is to be understood as an isocyclic, mono-, bi- orpolycyclic aromatic radical preferably having 6 to 14, in particular 6to 12, carbon atoms, such as phenyl, naphthyl or biphenylyl, preferablyphenyl.

The term “heterocyclyl” denotes a mono- or bicyclic radical which isfully saturated, partially or fully unsaturated and which contains oneto five identical or different atoms selected from the group consistingof nitrogen, sulfur and oxygen, where, however, two oxygen atoms may notbe directly adjacent and at least one carbon atom must be present in thering, for example a thienyl, furyl, pyrrolyl, thiazolyl, oxazolyl,imidazolyl, isothiazolyl, isoxazolyl, pyrazolyl, 1,3,4-oxadiazolyl,1,3,4-thiadiazolyl, 1,3,4-triazolyl, 1,2,4-oxadiazolyl,1,2,4-thiadiazolyl, 1,2,4-triazolyl, 1,2,3-triazolyl,1,2,3,4-tetrazolyl, benzo[b]thienyl, benzo[b]furyl, indolyl,benzo[c]thienyl, benzo[c]furyl, isoindolyl, benzoxazolyl,benzothiazolyl, benzimidazolyl, benzisoxazolyl, benzisothiazolyl,benzopyrazolyl, benzothiadiazolyl, benzotriazolyl, dibenzofuryl,dibenzothienyl, carbazolyl, pyridyl, pyrazinyl, pyrimidinyl,pyridazinyl, 1,3,5-triazinyl, 1,2,4-triazinyl, 1,2,4,5-tetrazinyl,quinolinyl, isoquinolinyl, quinoxalinyl, quinazolinyl,1,8-naphthyridinyl, 1,5-naphthyridinyl, 1,6-naphthyridinyl,1,7-naphthyridinyl, phthalazinyl, pyridopyrimidinyl, purinyl,pteridinyl, piperidinyl, pyrrolidinyl, oxazolinyl, tetrahydrofuryl,tetrahydropyranyl, isoxazolidinyl or thiazolidinyl radical.

A “hydrocarbon radical” is a straight-chain, branched or cyclichydrocarbon radical which may be saturated, partially saturated,unsaturated or aromatic, for example alkyl, alkenyl, alkynyl,cycloalkyl, cycloalkenyl, cycloalkylalkyl, aryl or CH₂aryl, preferablyalkyl, alkenyl and alkynyl having up to 20 carbon atoms or cycloalkylhaving 3 to 6 ring atoms or phenyl.

In the cases where two or more radicals R³ and/or R⁵ are present, i.e.if m and/or n are greater than one, these radicals may in each case beidentical or different.

If R¹ in the formula (I) is a hydrocarbon radical, this hydrocarbonradical has preferably up to 20 carbon atoms. If this hydrocarbonradical carries further carbon-containing substituents, the total numberof all carbon atoms of this radical R¹ is preferably 2 to 30.

Depending on the kind and the linkage of the substituents, the compoundsof formula (I) may be present as stereoisomers. If, for example, one ormore alkenyl groups are present, diastereomers may occur. If, forexample, one or more asymmetric carbon atoms are present, enantiomersand diastereomers may occur. Stereoisomers can be obtained from themixtures which are obtained in the preparation by customary separationmethods, for example by chromatographic separation processes. It is alsopossible to prepare stereoisomers selectively by employingstereoselective reactions using optically active starting materialsand/or auxiliaries. The process thus also relates to all stereoisomersand mixtures thereof which are embraced by the formula (I) but notspecifically defined.

The compounds of the formula (I) can form salts. Salt formation mayoccur by action of a base on those compounds of the formula (I) whichcarry an acidic hydrogen atom, for example in the case of R⁴=H. Suitablebases are, for example, organic amines and also ammonium, alkali metalor alkaline earth metal hydroxides, carbonates and bicarbonates, inparticular sodium hydroxide and potassium hydroxide, sodium carbonateand potassium carbonate and sodium bicarbonate and potassiumbicarbonate. Salt formation can also occur by addition of an acid tobasic groups, where a heterocyclyl group is present and represents abasic group such as imidazolyl or pyridyl. Acids which are suitable forthis purpose are inorganic and organic acids, for example HCl, HBr,H₂SO₄, HNO₃ or H₃PO₄, or acetic acid, trifluoroacetic acid or oxalicacid, or sulfonic acids, and the process of the invention includes theformation of such salts.

Preferably R¹ is hydrogen, (C₁-C₁₂)-alkyl, (C₂-C₈)-alkenyl,(C₂-C₈)-alkynyl, (C₃-C₈)-cycloalkyl, (C₃-C₈)-cycloalkenyl, aryl,—CH₂-aryl or —(CH₂)_(p)-heterocyclyl where heterocyclyl is a 3- to8-membered ring having up to three identical or different hetero atomsselected from the group consisting of nitrogen, oxygen and sulfur, wherethe eight last-mentioned radicals are unsubstituted or substituted byone or more radicals selected from the group consisting of halogen,(C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl, (C₁-C₆)-alkoxy, cyano and nitro.

Preferably also R¹ is hydrogen, (C₁-C₈)-alkyl, (C₂-C₆)-alkenyl,(C₂-C₆)-alkynyl, (C₃-C₆)-cycloalkyl, (C₅-C₆)-cycloalkenyl, phenyl or—(CH₂)_(p)-heterocyclyl where heterocyclyl is a 3- to 6-membered ringhaving up to three hetero atoms selected from the group consisting ofnitrogen, oxygen and sulfur, where the seven last-mentioned radicals areunsubstituted or substituted by one or more substituents selected fromthe group consisting of halogen, (C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl and(C₁-C₆)-alkoxy.

Preferably also R¹ is hydrogen, (C₁-C₆)-alkyl, (C₂-C₆)-alkenyl,(C₂-C₆)-alkynyl, (C₁-C₆)-alkoxy-(C₁-C₆)-alkyl, (C₃-C₆)-cycloalkyl,(C₃-C₆)-cycloalkyl-(C₁-C₆)-alkyl, —CH₂furyl, phenyl, —CH₂phenyl or—CH₂CH₂phenyl, which last three mentioned phenyl radicals areunsubstituted or substituted by one or more halogen radicals.

Preferably also R¹ is hydrogen, (C₁-C₆)-alkyl, (C₂-C₆)-alkenyl,(C₃-C₆)-cycloalkyl, (C₅-C₆)-cycloalkenyl, phenyl or 3- to 6-memberedheterocyclyl having up to three hetero atoms selected from the groupconsisting of nitrogen, oxygen and sulfur, where the six last-mentionedradicals are unsubstituted or substituted by one or more substituentsselected from the group consisting of halogen, (C₁-C₄)-alkyl,(C₁-C₄)-haloalkyl and (C₁-C₄)-alkoxy.

Preferably R² is hydrogen, (C₁-C₆)-alkyl or (C₁-C₆)-alkoxy where the twolast-mentioned radicals are unsubstituted or substituted by one or moreradicals selected from the group consisting of halogen and(C₁-C₄)-alkoxy.

Preferably also R² is hydrogen or (C₁-C₆)-alkyl or (C₁-C₆)-haloalkyl.

Preferably also R² is hydrogen, (C₁-C₆)-alkyl or (C₂-C₆)-alkynyl.

Preferably also R¹ and R² together form a —(CH₂)₂—O—(CH₂)₂—, —(CH₂)₄— or—(CH₂)₅— moiety.

Preferably R³ and R⁵ are each independently halogen, (C₁-C₆)-alkyl,(C₁-C₆)-haloalkyl, (C₁-C₆)-alkoxy, S(O)_(q)—(C₁-C₆)-alkyl, cyano ornitro, or R⁵ is —CO-aryl, or two adjacent R⁵ groups form a —O—CH₂CH₂—moiety.

Preferably also R³ and R⁵ are each independently halogen, (C₁-C₄)-alkyl,(C₁-C₄)-haloalkyl, (C₁-C₄)-alkoxy, S(O)_(q)—(C₁-C₄)-alkyl, cyano ornitro, or R⁵ is —CO-aryl, or two adjacent R⁵ groups form a —O—CH₂CH₂—moiety.

Preferably also R³ and R⁵ are each independently halogen, (C₁-C₄)-alkyl,(C₁-C₄)-haloalkyl, (C₁-C₄)-alkoxy, cyano or nitro, or R⁵ is —CO-aryl, ortwo adjacent R⁵ groups form a —O—CH₂CH₂— moiety.

Preferably, each R³ is independently halogen, (C₁-C₄)-alkyl,(C₁-C₄)-haloalkyl, (C₁-C₄)-alkoxy, S(O)_(q)—(C₁-C₄)-alkyl, cyano ornitro.

More preferably, each R³ independently is halogen, (C₁-C₄)-alkyl,(C₁-C₄)-haloalkyl, (C₁-C₄)-alkoxy, cyano or nitro.

More preferably, R³ is halogen or nitro.

Preferably R⁴ is hydrogen or (C₁-C₆)-alkyl.

More preferably R⁴ is hydrogen or (C₁-C₄)-alkyl.

Most preferably R⁴ is hydrogen.

Preferably, each R⁵ is independently halogen, (C₁-C₆)-alkyl,(C₁-C₆)-haloalkyl, (C₁-C₆)-alkoxy, S(O)_(q)—(C₁-C₆)-alkyl, cyano, nitro,—CO-aryl, or two adjacent R⁵ groups form a —O—CH₂CH₂— moiety, morepreferably is halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkoxy, nitro or—CO-naphthyl, or two adjacent R⁵ groups form a —O—CH₂CH₂— moiety.

More preferably, each R⁵ is independently halogen, (C₁-C₄)-alkyl,(C₁-C₄)-haloalkyl, (C₁-C₄)-alkoxy, S(O)_(q)—(C₁-C₄)-alkyl, cyano, nitroor —CO-aryl, or two adjacent R⁵ groups form a —O—CH₂CH₂— moiety, morepreferably is halogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkoxy, nitro or—CO-naphthyl, or two adjacent R⁵ groups form a —O—CH₂CH₂— moiety.

Preferably also R⁵ is each independently halogen, (C₁-C₄)-alkyl,(C₁-C₄)-haloalkyl, (C₁-C₄)-alkoxy, cyano or nitro, more preferablyhalogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkoxy, cyano or nitro, more preferably(C₁-C₄)-alkoxy.

Preferably n is 0, 1 or 2, more preferably 0.

Preferably m is 0, 1 or 2, more preferably 1 or 2, in particular 1.

Preferred compounds of formula (I) are those in which:

R¹ is hydrogen, (C₁-C₁₂)-alkyl, (C₂-C₈)-alkenyl, (C₂-C₈)-alkynyl,(C₃-C₈)-cycloalkyl, (C₃-C₈)-cycloalkenyl, aryl, —CH₂aryl or—(CH₂)_(p)-heterocyclyl where heterocyclyl is a 3- to 8-membered ringhaving up to three identical or different hetero atoms selected from thegroup consisting of nitrogen, oxygen and sulfur, where the eightlast-mentioned radicals are unsubstituted or substituted by one or moreradicals selected from the group consisting of halogen, (C₁-C₆)-alkyl,(C₁-C₆)-haloalkyl, (C₁-C₆)-alkoxy, cyano and nitro;R² is hydrogen, (C₁-C₆)-alkyl or (C₁-C₆)-alkoxy where the twolast-mentioned radicals are unsubstituted or substituted by one or moreradicals selected from the group consisting of halogen and(C₁-C₄)-alkoxy;R³ and R⁵ are each independently halogen, (C₁-C₆)-alkyl,(C₁-C₆)-haloalkyl, (C₁-C₆)-alkoxy, S(O)_(q)—(C₁-C₆)-alkyl, cyano ornitro, or R⁵ is —CO-aryl, or two adjacent R⁵ groups form a —O—CH₂CH₂—moiety; andR⁴ is hydrogen or (C₁-C₆)-alkyl.

Further preferred compounds of formula (I) are those in which:

R¹ is hydrogen, (C₁-C₈)-alkyl, (C₂-C₆)-alkenyl, (C₂-C₆)-alkynyl,(C₃-C₆)-cycloalkyl, (C₅-C₆)-cycloalkenyl, phenyl or—(CH₂)_(p)-heterocyclyl where heterocyclyl is a 3- to 6-membered ringhaving up to three hetero atoms selected from the group consisting ofnitrogen, oxygen and sulfur, where the seven last-mentioned radicals areunsubstituted or substituted by one or more substituents selected fromthe group consisting of halogen, (C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl and(C₁-C₆)-alkoxy;R² is hydrogen or (C₁-C₆)-alkyl or (C₁-C₆)-haloalkyl;R³ and R⁵ are each independently halogen, (C₁-C₄)-alkyl,(C₁-C₄)-haloalkyl, (C₁-C₄)-alkoxy, S(O)_(q)—(C₁-C₄)-alkyl, cyano ornitro, or R⁵ is —CO-aryl, or two adjacent R⁵ groups form a —O—CH₂CH₂—moiety; andR⁴ is hydrogen or (C₁-C₄)-alkyl.

Also preferred are compounds of formula (I) in which:

R¹ is hydrogen, (C₁-C₆)-alkyl, (C₂-C₆)-alkenyl, (C₂-C₆)-alkynyl,(C₁-C₆)-alkoxy-(C₁-C₆)-alkyl, (C₃-C₆)-cycloalkyl,(C₃-C₆)-cycloalkyl-(C₁-C₆)-alkyl, —CH₂furyl, phenyl, —CH₂phenyl or—CH₂CH₂phenyl, which last three mentioned phenyl radicals areunsubstituted or substituted by one or more halogen radicals;R² is hydrogen, (C₁-C₆)-alkyl or (C₂-C₆)-alkynyl;or R¹ and R² together form a —(CH₂)₂—O—(CH₂)₂—, —(CH₂)₄— or —(CH₂)₅—moiety;R³ is halogen or nitro;R⁴ is hydrogen or (C₁-C₄)-alkyl;R⁵ is halogen, (C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl, (C₁-C₆)-alkoxy,S(O)_(q)—(C₁-C₆)-alkyl, cyano, nitro, —CO-aryl, or two adjacent R⁵groups form a —O—CH₂CH₂— moiety, more preferably is halogen,(C₁-C₆)-alkyl, (C₁-C₆)-alkoxy, nitro or —CO-naphthyl, or two adjacent R⁵groups form a —O—CH₂CH₂— moiety;n is 0, 1 or 2; andm is 0, 1 or 2, more preferably 1 or 2.

Further preferred compounds of formula (I) are those in which:

R¹ is hydrogen, (C₁-C₆)-alkyl, (C₂-C₆)-alkenyl, (C₃-C₆)-cycloalkyl,(C₅-C₆)-cycloalkenyl, phenyl or 3- to 6-membered heterocyclyl having upto three hetero atoms selected from the group consisting of nitrogen,oxygen and sulfur, where the six last-mentioned radicals areunsubstituted or substituted by one or more substituents selected fromthe group consisting of halogen, (C₁-C₄)-alkyl, (C₁-C₄)-haloalkyl and(C₁-C₄)-alkoxy;R² is hydrogen, (C₁-C₆)-alkyl or (C₁-C₆)-haloalkyl;R³ and R⁵ are each independently halogen, (C₁-C₄)-alkyl,(C₁-C₄)-haloalkyl, (C₁-C₄)-alkoxy, cyano or nitro;R⁴ is hydrogen;n is 0, 1 or 2; andm is 0, 1 or 2, more preferably 1 or 2.

Particularly preferred compounds of formula (I) are those in which:

R¹ is hydrogen, (C₁-C₆)-alkyl or (C₃-C₆)-cycloalkyl;

R² and R⁴ are each hydrogen;

R⁵ is (C₁-C₆)-alkoxy;

n is 0;

m is 0 or 1; more preferably 1.

and the sulfamoyl group is located para to the CONR¹R² moiety in thephenyl ring.

Also preferred are processes for the preparation of formulae (Ia), (Ib),(Ic), (IVa), (IVb) and (IVc) as shown and defined in Tables 1 to 6below, wherein the radicals R¹, R², R³, R⁴, R⁵ and n are as definedabove, and preferably the preferred meanings above.

Compounds of formula (IV) are novel and form a further feature of theinvention. Compounds of formula (II), (III), (V) and (VI) are known ormay be prepared by known methods.

Compared with the known process, the present invention provides anoverall process for the preparation of acylsulfamoylbenzamides which hasfewer reaction steps, and gives higher yields and higher purity product.

The following non-limiting examples illustrate the invention.

The amounts, relative amounts, percentages or ratios refer to the weightunless another definition is specifically given.

EXAMPLE 1 4-[[(2-Methoxy-5-chlorobenzoyl)amino]sulfonyl]benzoyl chloride

A mixture of 4-aminosulfonylbenzoic acid (1 mol),2-methoxy-5-chlorobenzoic acid (1 mol) and thionyl chloride (2.5 mol) inchlorobenzene (700 ml) was heated at 120° C. for 7-9 hours. After thereaction was complete 200 ml of the solvent was removed in vacuo. Themixture was cooled and the precipitate filtered off and washed withheptane to give the title compound, mp. 138-140° C., yield 93% oftheory. 4-[[(Benzoyl)amino]sulfonyl]benzoyl chloride was prepared in asimilar manner from 4-aminosulfonylbenzoic acid and benzoic acid, mp.180-182° C., yield 96% of theory.4-[[(2-Chlorobenzoyl)amino]sulfonyl]benzoyl chloride was prepared in asimilar manner from 4-aminosulfonylbenzoic acid and 2-chlorobenzoicacid, mp. 198-200° C., yield 95% of theory.

EXAMPLE 2 N,N-Diethyl-4-[[(2-methoxybenzoyl)amino]sulfonyl]benzamide

To a suspension of 4-[[(2-methoxybenzoyl)amino]sulfonyl)benzoyl chloride(1 mol) and diethylamine (1 mol) in acetonitrile (1000 ml), was addedtriethylamine (1 mol) at 10° C. The mixture was stirred for 2 hours at20° C. and diluted with water (500 ml). The white precipitate wasfiltered off, washed and dried to give the title compound. The yield ofproduct obtained was 98% of theory, and the purity 98%.

EXAMPLE 3 N-Cyclopropyl-4-[[(2-chlorobenzoyl)amino]sulfonyl]benzamide

By employing the procedure described in Example 2 but using potassiumcarbonate (1 equivalent) instead of triethylamine, there was obtainedthe title compound in a yield of 99% of theory.

In the Tables 1 to 3 below are listed a number of examples of compoundsof formula (I) which are prepared by the process of the invention.

The abbreviations in the tables 1 to 6 denote:

-   Bu=n-butyl Et=ethyl-   Me=methyl c=cyclo-   Pr=n-propyl s=secondary-   i=iso Mp=melting point-   t=tertiary

If an alkyl radical is listed in the tables without any furtherspecification, this alkyl radical is straight-chain.

TABLE 1 (Ia)

Cpd Yield Mp No. R¹ R² R³ R⁴ R⁵ % ° C. 1-1 Et Et — H 2-OMe 94-98 1-2 BuH — H 2-OMe, 5-Me 92-96 196 1-3 Bu H — H 2-NO₂, 4-Cl 86-90 1-4 Bu H — H2,5-(Me)₂ 83-87 1-5 Bu H — H 2,3-(Me)₂ 86-90 1-6 Bu H — H 2-NO₂, 4-Cl76-80 1-7 Bu H — Me 2-OMe 85-89 1-8 Bu H — Me 2-OMe, 5-Me 81-85 1-9 Bu H— Me 2-Cl 86-90 1-10 Et Et — Me 2-OMe, 5-Cl 93-97 1-11 Bu H 2-NO₂ H2-OMe 93-97 1-12 Bu H 2-NO₂ H 2-OMe, 5-Me 1-13 Bu H 2-NO₂ H 2-Cl 93-971-14 Bu H 2-NO₂ H 2-OMe, 5-Cl 81-85 1-15 Pr H — H 2-OMe 1-16 Pr H — H2-Me 93-97 120 1-17 Pr H — H 2-Cl 1-18 Pr H — H 2-OMe, 5-Me 1-19 Pr H —H 2-OMe, 5-Cl 1-20 Pr H — H 2,3-(Me)₂ 1-21 Pr H — H 2-NO₂, 4-Cl 1-22 PrH 2-NO₂ H 2-OMe, 5-Cl 1-23 Pr H 2-NO₂ H 2,3-(Me)₂ 93-97 1-24 Pr H 2-NO₂H 2-OMe 93-97 197 1-25 Pr H — Me 2-OMe, 5-Cl 1-26 Pr H — Me 2,3-(Me)₂81-85 1-27 Pr H — Me 2-OMe, 5-Me 1-28 Pr H — Me 2-OMe 93-97 1-29 Pr H2-NO₂ Me 2-OMe, 5-Me 1-30 allyl H 2-NO₂ H 2-OMe 81-85 1-31 allyl H — Me2,5-(Me)₂ 1-32 allyl H — Me 2-OMe, 5-Me 93-97 1-33 allyl H — H 2-NO₂,4-Cl 1-34 allyl Allyl — H 2-OMe, 5-Me 1-35 allyl Allyl — H 2-Cl 1-36allyl Me — H 2-Me 1-37 allyl Me — H 2-OMe 1-38 allyl Me — H 2-OMe, 5-Me1-39 allyl Me — H 2-OMe, 5-Cl 93-97 214 1-40 Allyl Me — H 2,3-(Me)₂ 1-41c-hexyl H — H 2-Cl 93-97 1-42 c-hexyl H 2-NO₂ H 2-OMe, 5-Me 1-43c-pentyl H 2-NO₂ H 2-OMe, 5-Me 1-44 c-pentyl H — Me 2-OMe, 5-Me 93-971-45 c-Pr H — H 2-OMe 96-100 217 1-46 c-Pr H — H 2-Cl 96-100 207 1-47c-Pr H — H 2-Me 88-92 226 1-48 c-Pr H — H 2-OMe, 5-Me 88-92 211 1-49c-Pr H — H 2,3-(Me)₂ 88-92 233 1-50 c-Pr H — H 2,5-(Me)₂ 93-97 225 1-51c-Pr H — Me 2-OMe 88-92  70 1-52 c-Pr H — Me 2-Me 92-96 122 1-53 c-Pr H— Me 2,5-(Me)₂ 92-96 1-54 c-Pr H — Me 2-OMe, 5-Me 1-55 c-Pr H 2-NO₂ H2-OMe, 5-Me 1-56 C₂H₄—OEt H — H 2-Cl 92-96 138 1-57 C₂H₄—OEt H — H 2-OMe1-58 C₂H₄—OEt H — H 2-Me 92-96 162 1-59 C₂H₄—OEt H — H 2-OMe 1-60C₂H₄—OEt H — H 2-Cl 92-96 163 1-61 C₂H₄—OEt H — H 2,5-(Me)₂ 1-62C₂H₄—OEt H — H 2,5-Cl₂ 92-96 185 1-63 C₂H₄—OEt H — H 2,3-(Me)₂ 1-64C₂H₄—OEt H — H 2-OMe, 5-Cl 92-96 193 1-65 C₂H₄—OEt H — Me 2,3-(Me)₂92-96 1-66 C₂H₄—OEt H — Me 2-Me 91-95 1-67 C₂H₄—OEt H — Me 2-OMe, 5-Me1-68 C₃H₆—OMe H — H 2-Me 92-96  93 1-69 C₃H₆—OMe H — H 2-Cl 1-70CH₂-2-furanyl H — H 2-Me 92-96 205 1-71 CH₂-2-furanyl H — H 2-OMe 91-95190 1-72 CH₂-c-Pr H — H 2,5-Cl₂ 91-95 209 1-73 CH₂-c-Pr H — H 2,5-(Me)₂1-74 CH₂-c-Pr H — H 2-Me 1-75 CH₂-c-Pr H — H 2-OMe, 5-Me 1-76 CH₂-c-Pr H— H 2-OMe, 5-Cl 1-77 CH₂-c-Pr H — H 2-Cl 1-78 CH₂C≡CH H — H 2,5-Cl₂92-96 175 1-79 CH₂C≡CH H — Me 2,5-(Me)₂ 88-92 185 1-80 CH₂C≡CH CH₂C≡CH —Me 2-OMe, 5-Me 88-92 1-81 CH₂-t-Bu H — H 2-Cl 88-92 213 1-82 CH₂-t-Bu H— H 2-OMe 1-83 CH₂-t-Bu H — H 2-Me 1-84 CH₂CH(OMe)₂ H — H 2-OMe 1-85CH₂CH(OMe)₂ H — H 2-Me 88-92 140 1-86 Et Et — H 2-OMe 1-87 Et Et — H2-Cl 1-88 Et Et — H 2,5-Cl₂ 88-92 155 1-89 Et Et — H 2-OMe 88-92 1-90 EtH — H 2,5-(Me)₂ 1-91 Et H — H 2,3-(Me)₂ 88-92 1-92 Et H — Me 2-OMe 1-93Et H — Me 2-OMe, 5-Me 1-94 Et H 2-NO₂ H 2-OMe, 5-Me 88-92 1-95 i-Bu H —H 2-OMe 1-96 i-Bu H — H 2-Me 88-92 150 1-97 i-Bu H — H 2-Cl 1-98 i-Bu H— H 2,3-(Me)₂ 1-99 i-Bu H — H 2-OMe, 5-Me 1-100 i-Bu H — H 2,5-(Me)₂1-101 i-Pr H — H 2-Me 88-92 200 1-102 i-Pr H — H 2-OMe 1-103 i-Pr H — H2-Cl 1-104 i-Pr H — H 2,4-Cl₂ 88-92 258 1-105 i-Pr H — H 2,5-Cl₂ 1-106i-Pr H — Me 2-OMe, 5-Me 1-107 i-Pr H — Me 2,5-(Me)₂ 1-108 i-Pr H — H2-NO₂, 4-Cl 1-109 i-Pr H 2-NO₂ H 2-Me 1-110 i-Pr H 2-NO₂ H 2-OMe, 5-Me1-111 i-Pr H 2-NO₂ H 2,5-(Me)₂ 1-112 Me H — H 2,3-(Me)₂ 88-92 227 1-113Me H — H 2,5-Cl₂ 1-114 Me H — H 2-Me 1-115 Me H — H 2-OMe, 5-Me 1-116 MeH — H 2,5-(Me)₂ 1-117 Me H — H 2-NO₂, 4-Cl 88-92 1-118 Me H — H 2-Cl1-119 Me H 2-NO₂ H 2-OMe, 5-Me 1-120 Me H — Me 2,5-(Me)₂ 1-121 Me Et — H2-Cl 88-92 188 1-122 Me Et — H 2-OMe 1-123 Me Et — H 2-Me 1-124 Me Et —H 2-NO₂, 4-Cl 88-92 1-125 Me Et — H 2-OMe, 5-Me 1-126 Me Et 2-NO₂ H2-OMe, 5-Me 1-127 Me Et — Me 2,5-(Me)₂ 1-128 Me Me — H 2-OMe 1-129 Me Me— H 2-Me 1-130 Me Me — H 2-Cl 1-131 Me Me — H 2-OMe, 5-Me 1-132 Me Me —H 2,5-(Me)₂ 1-133 Me Me — H 2,3-(Me)₂ 88-92 205 1-134 Me Allyl — H 2-Cl1-135 —(CH₂)₂—O—(CH₂)₂— — H 2-OMe 1-136 —(CH₂)₂—O—(CH₂)₂— — H 2-OMe,5-Me 1-137 —(CH₂)₂—O—(CH₂)₂— — H 2-Cl 1-138 —(CH₂)₄— — H 2-NO₂, 4-Cl1-139 —(CH₂)₅— — H 2,5-(Me)₂ 88-92 157 1-140 —(CH₂)₅— — H 2,5-Cl₂ 1-141—(CH₂)₅— — H 2-OMe, 5-Cl 1-142 —(CH₂)₅— — H 2-NO₂, 4-Cl 1-143 —C₂H₄—C₆H₅H — H 2-OMe, 5-Me 1-144 —C₂H₄—C₆H₅ H — H 2-OMe, 5-Cl 1-145 —C₂H₄—C₆H₅ H— H 2-OMe 1-146 —(CH₂)₄— — Me 2-OMe, 5-Cl 1-147 Me Et — Me 2-OMe 1-148Pr Pr — H 2-OMe, 5-Cl 1-149 Pr Pr — H 2,5-(Me)₂ 1-150 Et H — H 2-OMe1-151 Et H — H 2-OMe, 5-Cl 1-152 CH₂C≡CH CH₂C≡CH — H 2-OMe, 5-Cl 1-153CH(CH₃)—C₃H₇ H — H 2-OMe, 5-Cl 1-154 c-Pr H — H 2-O—CH₂CH₂-3 1-155 s-BuH — H 2-OMe, 5-Cl 1-156 s-Bu H — H 2-OMe 1-157 2-heptyl H — H 2-OMe,5-Cl 1-158 2-heptyl H — H 2-OMe 1-159 Me Me — H 2-OMe, 5-Cl 1-160 Me Et— Me 2-Me 1-161 c-Pr H 2-NO₂ H 2-OMe 1-162 Pr H 2-Cl H 2-Me 1-163 c-Pr H2-Cl H 2-OMe

TABLE 2 (Ib)

Cpd Yield Mp No. R¹ R² R³ R⁴ R⁵ % ° C. 2-1 Pr H 2,4-Cl₂ H 2,5-(Me)₂ 2-2Pr H 2,4-Cl₂ H 2-OMe 2-3 Pr H 2,4-Cl₂ H 2-Cl 2-4 Pr H 2,4-Cl₂ H 2-Me86-90 2-5 Pr H 2,4-Cl₂ H 2,3-(Me)₂ 85-89 2-6 Pr H 2,4-Cl₂ H 2-OMe, 5-Me84-88 2-7 Pr H 2,4-Cl₂ H 2-NO₂, 4-Cl 84-88 2-8 Pr H 2,4-Cl₂ Me 2-OMe,5-Me 83-87 2-9 Pr H H H 2-OMe, 5-Me 2-10 Pr H H H 2-OMe, 5-Cl 76-80 2-11Pr H H H 2-OMe 2-12 Pr H H H 2,5-(Me)₂ 76-80 2-13 Bu H 2,4-Cl₂ H2,5-(Me)₂ 2-14 Bu H 2,4-Cl₂ H 2-OMe, 5-Me 2-15 Bu H 2,4-Cl₂ H 2-OMe,5-Cl 2-16 Bu H H H 2-OMe, 5-Me 2-17 Bu H H H 2-OMe, 5-Cl 2-18 Bu H H H2-OMe 2-19 Bu H H H 2,5-(Me)₂ 2-20 Me H 4-Cl H 2-Cl 2-21 Me H 4-Cl H2-Me 2-22 Me H 4-Cl H 2,3-(Me)₂ 87-91 215 2-23 Me Me 2,4-Cl₂ H 2-OMe,5-Me 2-24 Me Me 2,4-Cl₂ H 2-OMe, 5-Cl 2-25 Me Me 2,4-Cl₂ H 2-NO₂, 4-Cl2-26 Me Me 4-Cl H 2-OMe, 5-Me 2-27 Me Me 4-Cl H 2-OMe, 5-Cl 2-28 Me Me4-Cl H 2-NO₂, 4-Cl 87-91 2-29 Me Me 4-Cl Me 2-OMe, 5-Me 2-30 Me Me H H2-OMe, 5-Me 2-31 Me Me H H 2-NO₂, 4-Cl 2-32 Me Me H H 2-OMe 2-33C₂H₄—OMe H 2,4-Cl₂ H 2-OMe 2-34 C₂H₄—OMe H 2,4-Cl₂ H 2-Me 2-35 C₂H₄—OMeH 2,4-Cl₂ H 2,5-(Me)₂ 2-36 C₂H₄—OMe H 2,4-Cl₂ H 2-Cl 2-37 C₂H₄—OMe H2,4-Cl₂ H 2,5-Cl₂ 2-38 c-Pr H 2,4-Cl₂ H 2,5-(Me)₂ 2-39 c-Pr H 2,4-Cl₂ H2-OMe 84-88 174 2-40 c-Pr H 2,4-Cl₂ H 2-Cl 2-41 c-Pr H 2,4-Cl₂ H 2-Me2-42 c-Pr H 4-Cl H 2-OMe 2-43 c-Pr H 4-Cl H 2-Me 2-44 c-Pr H 2,4-Cl₂ H2,5-Cl₂ 2-45 c-Pr H 2,4-Cl₂ H 2,3-(Me)₂ 83-87 2-46 c-Pr H 2,4-Cl₂ H2-OMe, 5-Me 2-47 c-Pr H 2,4-Cl₂ H 2-OMe, 5-Cl 2-48 c-Pr H 2,4-Cl₂ H2-NO₂, 4-Cl 2-49 c-Pr H 4-Cl H 2-Cl 2-50 c-Pr H 4-Cl H 2,5-(Me)₂ 2-51c-Pr H 4-Cl H 2-OMe, 5-Me 83-87 2-52 c-Pr H 4-Cl H 2-OMe, 5-Cl 2-53 c-PrH 4-Cl H 2-NO₂, 4-Cl 2-54 c-Pr H 4-Cl Me 2-OMe, 5-Me 2-55 c-Pr H H H2,5-(Me)₂ 2-56 c-Pr H H H 2-OMe, 5-Me 76-80 2-57 c-Pr H H H 2-OMe, 5-Cl2-58 c-Pr H H H 2-NO₂, 4-Cl 2-59 allyl H 2,4-Cl₂ H 2-OMe 2-60 allyl H2,4-Cl₂ H 2-Cl 2-61 CH₂C≡CH H 2,4-Cl₂ H 2,5-(Me)₂ 2-62 CH₂C≡CH H 2,4-Cl₂H 2-OMe, 5-Me 2-63 CH₂C≡CH H 2,4-Cl₂ H 2-OMe, 5-Cl 2-64 CH₂C≡CH H2,4-Cl₂ H 2-NO₂, 4-Cl 2-65 CH₂C≡CH H 2,4-Cl₂ Me 2-OMe, 5-Me 2-66 CH₂C≡CHH 4-Cl H 2,5-(Me)₂ 2-67 CH₂C≡CH H 4-Cl H 2-OMe, 5-Me 2-68 CH₂C≡CH H 4-ClH 2-OMe, 5-Cl 2-69 CH₂C≡CH H 4-Cl H 2-NO₂, 4-Cl 2-70 —(CH₂)₄— 2,4-Cl₂ H2,5-(Me)₂ 2-71 —(CH₂)₄— 2,4-Cl₂ H 2-OMe, 5-Me 2-72 —(CH₂)₄— 2,4-Cl₂ H2-OMe, 5-Cl 2-73 —(CH₂)₄— 2,4-Cl₂ H 2-NO₂, 4-Cl 2-74 —(CH₂)₄— H H 2-OMe,5-Cl 2-75 —(CH₂)₄— H H 2-OMe 2-76 Me Et H H 2-OMe, 5-Cl 2-77 Me Et H H2-OMe 2-78 i-Pr H H H 2,5-(Me)₂ 2-79 Me H H H 2-OMe 2-80 Me H H H2,5-(Me)₂

TABLE 3 (Ic)

Cpd Yield Mp No. R¹ R² R³ R⁴ R⁵ % ° C. 3-1 Pr H H H 2,5-(Me)₂ 3-2 Pr H HH 2-OMe 3-3 Pr H H H 2-Cl 3-4 Pr H H H 2-Me 3-5 Pr H H H 2,3-(Me)₂ 3-6Pr H H H 2-OMe, 5-Me 3-7 Pr H H H 2-OMe, 5-Cl 3-8 Pr H H H 2-NO₂, 4-Cl3-9 Pr H H Me 2-OMe, 5-Me 3-10 Pr H 2-Cl H 2-OMe, 5-Me 3-11 Pr H 2-Cl H2,5-(Me)₂ 3-12 Bu H H H 2,5-(Me)₂ 3-13 Bu H H H 2-OMe, 5-Me 3-14 Bu H HH 2-OMe, 5-Cl 3-15 Bu H H H 2-NO₂, 4-Cl 3-16 Bu H 2-Cl H 2-OMe, 5-Me3-17 Bu H 2-Cl H 2-OMe, 5-Cl 3-18 Bu H 2-Cl H 2-OMe 3-19 Bu H 2-Cl H2,5-(Me)₂ 3-20 Me H 2-Cl H 2-Cl 3-21 Me H 2-Cl H 2-Me 3-22 Me H 2-Cl H2,3-(Me)₂ 3-23 Me Me H H 2-OMe, 5-Me 3-24 Me Me H H 2-OMe, 5-Cl 3-25 MeMe H H 2-NO₂, 4-Cl 3-26 Me Me 2-Cl H 2-OMe, 5-Me 3-27 Me Me 2-Cl H2-OMe, 5-Cl 3-28 Me Me 2-Cl H 2-NO₂, 4-Cl 3-29 Me Me 2-Cl Me 2-OMe, 5-Me3-30 Me Me 4-NO₂ H 2-OMe, 5-Me 3-31 Me Me 4-NO₂ H 2-OMe 3-32 C₂H₄—OMe HH H 2-OMe 3-33 C₂H₄—OMe H H H 2,5-Cl₂ 3-34 c-Pr H H H 2,5-(Me)₂ 3-35c-Pr H H H 2-OMe 3-36 c-Pr H H H 2-Cl 3-37 c-Pr H H H 2-Me 3-38 c-Pr H2-Cl H 2-OMe 3-39 c-Pr H 2-Cl H 2-Me 3-40 c-Pr H 2-Cl H 2-Cl 3-41 c-Pr H2-Cl H 2,5-(Me)₂ 3-42 c-Pr H 2-Cl H 2-OMe, 5-Me 3-43 c-Pr H 2-Cl H2-NO₂, 4-Cl 3-44 c-Pr H 2-Cl Me 2-OMe, 5-Me 3-45 allyl H H H 2-OMe 3-46allyl H H H 2-Cl 3-47 allyl H H H 2,5-(Me)₂ 3-48 allyl H H H 2,5-Cl₂3-49 CH₂C≡CH H H H 2,5-(Me)₂ 3-50 CH₂C≡CH H H H 2-OMe, 5-Me

Tables 4 to 6 list some examples of compounds of formula (IV) which areprepared:

TABLE 4 (IVa)

Cpd Yield Mp No. R³ R⁴ R⁵ % ° C. 4-1 — H — 94-98 182 4-2 — H 2,3-(Me)₂90-94 4-3 — H 2,4-Cl₂ 94-98 4-4 — H 2,5-Cl₂ 90-94 140 4-5 — H 2,5-(Me)₂89-93 4-6 — H 2-Cl 93-97 198 4-7 — H 2-Me 92-96 4-8 — H 2-NO₂, 4-Cl90-94 178 4-10 — H 2-OMe 92-96 126 4-11 — H 2-OMe, 5-Cl 91-95 138-1404-12 2-Cl H 2-OMe, 5-Me 88-92 160-163 4-13 3-Cl H 2-OMe, 5-Cl 90-94 1654-14 — Me 2,3-(Me)₂ 93-97 4-15 — Me 2,5-(Me)₂ 88-92 4-17 — Me 2-Me 93-974-18 — Me 2-OMe 88-92 4-19 — Me 2-OMe, 5-Cl 93-97 4-20 — Me 2-OMe, 5-Me88-92 4-21 2-Cl H 2-Me 93-97 4-22 2-Cl H 2-OMe 88-92 128 4-23 2-Cl H2-OMe, 5-Cl 90-94 4-24 2-NO₂ H 2,3-(Me)₂ 93-97 4-25 2-NO₂ H 2,5-(Me)₂93-97 4-26 2-NO₂ H 2-Cl 88-92 4-27 2-NO₂ H 2-Me 93-97 130 4-28 2-NO₂ H2-OMe 90-94 123 4-29 2-NO₂ H 2-OMe, 5-Cl 88-92 112 4-30 2-NO₂ H 2-OMe,5-Me 90-94 125 4-31 2-NO₂ H 2-OMe, 5-Me 88-92 139

TABLE 5 (IVb)

Cpd Yield Mp No. R³ R⁴ R⁵ % ° C. 5-1 2,4 Cl2 H 2-NO₂, 4-Cl 5-2 2,4-Cl2 H2,3-(Me)₂ 86-90 5-3 2,4-Cl2 H 2,5-(Me)₂ 5-4 2,4-Cl2 H 2-Cl 76-80 5-62,4-Cl2 H 2-NO₂, 4-Cl 5-7 2,4-Cl2 H 2-OMe 87-91 5-8 2,4-Cl2 H 2-OMe,5-Cl 82-86 5-9 2,4-Cl2 H 2-OMe, 5-Me 77-81 5-10 2,4-Cl2 Me 2-OMe, 5-Me5-11 2,4-Cl2 H 2,3-(Me)₂ 75-79 5-15 2,4-Cl2 H 2-Me 5-16 2,4-Cl2 H 2-NO₂,4-Cl 5-17 2,4-Cl2 H 2-OMe 5-18 2,4-Cl2 H 2-OMe, 5-Cl 82-86 5-19 2,4-Cl2H 2-OMe, 5-Me 5-20 2,4-Cl2 Me 2-OMe, 5-Me 5-21 4-Cl H 2,3-(Me)₂ 82-865-22 4-Cl H 2,5-(Me)₂ 5-23 4-Cl H 2-Cl 74-78 5-24 4-Cl H 2-Me 5-25 4-ClH 2-NO₂, 4-Cl 5-26 4-Cl H 2-OMe 76-80 5-27 4-Cl H 2-OMe, 5-Cl 5-29 4-ClMe 2-OMe, 5-Me 82-86 5-31 — H 2-NO₂, 4-Cl 5-32 — H 2-OMe 81-85 5-33 — H2-OMe, 5-Cl 5-34 — H 2-OMe, 5-Me 82-86

TABLE 6 (IVc)

Cpd Yield Mp No. R³ R⁴ R⁵ % ° C. 6-1 2-Cl H 2,3-(Me)₂ 81-85 180-185 6-22-Cl H 2,5-(Me)₂ 93-97 102 6-3 2-Cl H 2-Cl 92-96 110 6-4 2-Cl H 2-Me88-92 6-6 2-Cl H 2-OMe 93-97 118 6-7 2-Cl H 2-OMe, 5-Cl 91-95 6-8 2-Cl H2-OMe, 5-Me 87-91 6-9 2-Cl Me 2-OMe, 5-Me 87-91  98 6-10 4-NO₂ H 2-NO₂,4-Cl 89-93 6-13 4-NO₂ H 2-OMe, 5-Me 90-94 6-16 — H 2,5-Cl₂ 89-93 6-17 —H 2-Cl 92-96 6-18 — H 2-Me 91-95 6-19 — H 2-NO₂, 4-Cl 88-92 6-20 — H2-OMe 88-92 6-21 — H 2-OMe, 5-Cl 88-92 6-22 — H 2-OMe, 5-Me 88-92 6-23 —Me 2-OMe, 5-Me 88-92

1. A compound of formula (IV):

in which R³ and R⁵ are each independently halogen, (C₁-C₆)-alkyl,(C₁-C₆)-haloalkyl, (C₁-C₆)-alkoxy, S(O)_(q)—(C₁-C₆)-alkyl,(C₁-C₆)-alkylcarbonyl, —CO-aryl, cyano or nitro; or two adjacent R⁵groups form a —O—CH₂CH₂— moiety, R⁴ is hydrogen, (C₁-C₄)-alkyl,(C₂-C₄)-alkenyl or (C₂-C₄)-alkynyl, n is an integer from 0 to 4, m is aninteger from 0 to 5, and q is 0, 1 or 2; or a salt thereof.
 2. Acompound or a salt thereof as claimed in claim 1, wherein R³ is eachindependently halogen, (C₁-C₄)-alkyl, (C₁-C₄)-haloalkyl, (C₁-C₄)-alkoxy,S(O)_(q)—(C₁-C₄)-alkyl, cyano or nitro, R⁴ is hydrogen or (C₁-C₄)-alkyl,R⁵ is each independently halogen, (C₁-C₄)-alkyl, (C₁-C₄)-haloalkyl,(C₁-C₄)-alkoxy, cyano or nitro, n is 0, 1 or 2, m is 0 or 1 or 2, and qis 0, 1 or
 2. 3. A compound or a salt thereof as claimed in claim 1,wherein R⁴ is hydrogen, R³ is (C₁-C₆)-alkoxy, n is 0, m is 0 or 1, andthe sulfamoyl group is located para to the COCl moiety in the phenylring.
 4. A compound or a salt thereof as claimed in claim 1, wherein R⁴is hydrogen, R⁵ is (C₁-C₄)-alkoxy, n is 0, m is 1, and the sulfamoylgroup is located para to the COCl moiety in the phenyl ring.
 5. Aprocess for the preparation of a compound of formula (IV), or a saltthereof, as defined in claim 1, which comprises reaction of a compoundof formula (II):

wherein R³, R⁴ and n are as defined in formula (IV), with a compound offormula (III):

wherein R⁵ and m are as defined in formula (IV) and Y is OH or Cl, inthe presence of a chlorinating agent.
 6. A process as claimed in claim 5wherein Y is OH.
 7. A process as claimed in claim 5 wherein thechlorinating agent is thionylchloride.
 8. A process as claimed in claim5 wherein the amount of chlorinating agent used is, when Y is OH from 1to 2 molar equivalents per equivalents of (II) and (IIIa), or when Y isCl from 1 to 2 molar equivalents per equivalent of (II).
 9. A process asclaimed in claim 5, wherein the solvent used in the reaction of thecompound of formula (II) with the compound of formula (III) ischlorobenzene.
 10. A process for the preparation of a compound offormula (I) or a salt thereof,

wherein: R¹ is hydrogen, —(CH₂)_(p)-heterocyclyl or a hydrocarbonradical, where the two last-mentioned radicals are unsubstituted orsubstituted by one or more radicals selected from the group consistingof halogen, (C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl, (C₁-C₆)-alkoxy, cyano andnitro; R² is hydrogen, (C₁-C₆)-alkyl, (C₂-C₆)-alkenyl, (C₂-C₆)-alkynyl,(C₁-C₆)-alkoxy, (C₂-C₆)-alkenyloxy, where the five last-mentionedradicals are unsubstituted or substituted by one or more radicalsselected from the group consisting of halogen, (C₁-C₄)-alkoxy and(C₁-C₄)-alkylthio; or R¹ and R² together with the linking nitrogen atomform a 3- to 8-membered saturated or unsaturated ring; R³ and R⁵ areeach independently halogen, (C₁-C₆)-alkyl, (C₁-C₆)-haloalkyl,(C₁-C₆)-alkoxy, S(O)_(q)—(C₁-C₆)-alkyl, (C₁-C₆)-alkylcarbonyl, —CO-aryl,cyano or nitro; or two adjacent R⁵ groups form a —O—CH₂CH₂— moiety; R⁴is hydrogen, (C₁-C₄)-alkyl, (C₂-C₄)-alkenyl or (C₂-C₄)-alkynyl; n is aninteger from 0 to 4; m is an integer from 0 to 5; p is 0 or 1; and q is0, 1 or 2; or a salt thereof, which process comprises the reaction of acompound of formula (IV),

in which R³, R⁴, R⁵ m and n are defined as in formula (I), with acompound of formula (V):R¹R²NH  (V) wherein R¹, R², R³, R⁴, R⁵, m and n are as defined informula (I), in the presence of a base.
 11. A process as claimed inclaim 10, wherein R³ is each independently halogen, (C₁-C₄)-alkyl,(C₁-C₄)-haloalkyl, (C₁-C₄)-alkoxy, S(O)_(q)—(C₁-C₄)-alkyl, cyano ornitro, R⁴ is hydrogen or (C₁-C₄)-alkyl, R⁵ is each independentlyhalogen, (C₁-C₄)-alkyl, (C₁-C₄)-haloalkyl, (C₁-C₄)-alkoxy, cyano ornitro, n is 0, 1 or 2, m is 0 or 1 or 2, and q is 0, 1 or
 2. 12. Aprocess as claimed in claim 10, wherein R⁴ is hydrogen, R⁵ is(C₁-C₆)-alkoxy, n is 0, m is 0 or 1, and the sulfamoyl group is locatedpara to the COCl moiety in the phenyl ring.
 13. A compound or a saltthereof as claimed in claim 1, wherein R³ is (C₅-C₆)-haloalkyl,S(O)_(q)—(C₁-C₆)-alkyl, (C₅-C₆)-alkylcarbonyl, —CO-aryl; or two adjacentR⁵ groups form a —O—CH₂CH₂— moiety.
 14. A compound or a salt thereof asclaimed in claim 1, wherein R⁵ is (C₅-C₆)-haloalkyl,S(O)_(q)—(C₁-C₆)-alkyl, (C₅-C₆)-alkylcarbonyl, —CO-aryl; or two adjacentR⁵ groups form a —O—CH₂CH₂— moiety.
 15. A compound or a salt thereof asclaimed in claim 1, wherein R³ and R⁵ are each independently(C₅-C₆)-haloalkyl, S(O)_(q)—(C₁-C₆)-alkyl, (C₅-C₆)-alkylcarbonyl,—CO-aryl; or two adjacent R⁵ groups form a —O—CH₂CH₂— moiety.